Budesonide administered using chlorofluorocarbon and hydrofluoroalkane pressurized metered-dose inhalers: pharmacokinetics, pharmacodynamics and clinical equivalence

Singh, Dave; Tütüncü, Ahmet; Löhr, Iren Høyland; Carlholm, Marie; Polanowski, Tomasz

doi:10.5414/cpp45485

Cited by 3 publications

(1 citation statement)

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“…Second, many studies have shown that HFA pMDIs are pharmacokinetically and clinically comparable to or even superior to traditional CFC MDIs. 32 – 37 …”

Section: Discussionmentioning

confidence: 99%

Effect of salmeterol/fluticasone combination on the dynamic changes of lung mechanics in mechanically ventilated COPD patients: a prospective pilot study

Chen¹,

Chen²,

Chiang³

et al. 2016

COPD

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BackgroundThe combined therapy of inhaled corticosteroids and long-acting beta-2 agonists for mechanically ventilated patients with COPD has never been explored. Therefore, the aim of this study was to investigate their dynamic effects on lung mechanics and gas exchange.Materials and methodsTen mechanically ventilated patients with resolution of the causes of acute exacerbations of COPD were included. Four puffs of salmeterol 25 μg/fluticasone 125 μg combination therapy were administered. Lung mechanics, including maximum resistance of the respiratory system (Rrs), end-inspiratory static compliance, peak inspiratory pressure (PIP), plateau pressure, and mean airway pressure along with gas exchange function were measured and analyzed.ResultsSalmeterol/fluticasone produced a significant improvement in Rrs and PIP after 30 minutes. With regard to changes in baseline values, salmeterol/fluticasone inhalation had a greater effect on PIP than Rrs. However, the therapeutic effects seemed to lose significance after 3 hours of inhaled corticosteroid/long-acting beta-2 agonist administration.ConclusionThe combination of salmeterol/fluticasone-inhaled therapy in mechanically ventilated patients with COPD had a significant benefit in reducing Rrs and PIP.

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“…Second, many studies have shown that HFA pMDIs are pharmacokinetically and clinically comparable to or even superior to traditional CFC MDIs. 32 – 37 …”

Section: Discussionmentioning

confidence: 99%

Effect of salmeterol/fluticasone combination on the dynamic changes of lung mechanics in mechanically ventilated COPD patients: a prospective pilot study

Chen¹,

Chen²,

Chiang³

et al. 2016

COPD

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Real-time analysis of gene regulation by glucocorticoid hormones

McMaster

Chambers²,

Meng³

et al. 2008

Journal of Endocrinology

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There is increasing evidence that temporal factors are important in allowing cells to gain additional information from external factors, such as hormones and cytokines. We sought to discover how cell responses to glucocorticoids develop over time, and how the response kinetics vary according to ligand structure and concentration, and hence have developed a continuous gene transcription measurement system, based on an interleukin-6 (IL-6) luciferase reporter gene. We measured the time to maximal response, maximal response and integrated response, and have compared these results with a conventional, end point glucocorticoid bioassay. We studied natural glucocorticoids (corticosterone and cortisol), synthetic glucocorticoids (dexamethasone) and glucocorticoid precursors with weak, or absent bioactivity. We found a close correlation between half maximal effective concentration (EC50) for maximal response, and for integrated response, but with consistently higher EC50 for the latter. There was no relation between the concentration of ligand and the time to maximal response. A comparison between conventional end point assays and real-time measurement showed similar effects for dexamethasone and hydrocortisone, with a less effective inhibition of IL-6 seen with corticosterone. We profiled the activity of precursor steroids, and found pregnenolone, progesterone, 21-hydroxyprogesterone and 17-hydroxyprogesterone all to be ineffective in the real-time assay, but in contrast, progesterone and 21-hydroxyprogesterone showed an IL-6 inhibitory activity in the end point assay. Taken together, our data show how ligand concentration can alter the amplitude of glucocorticoid response, and also that a comparison between real-time and end point assays reveals an unexpected diversity of the function of glucocorticoid precursor steroids, with implications for human disorders associated with their overproduction.

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Switching from systemic steroids to ciclesonide restores the hypothalamic pituitary-adrenal axis

Marczak

Ciebiada

Górski

2014

pdia

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IntroductionTreatment of difficult asthma with oral corticosteroids (OCS) may suppress the hypothalamic-pituitary-adrenal axis.AimIn this study we have checked if the substitution of OCS with very high doses of ciclesonide may restore the adrenal function without losing the control of the disease.Material and methodsIn 5 patients with difficult, uncontrolled asthma despite treatment with OCS, inhaled and systemic glucocorticosteroids were replaced with very high doses of ciclesonide (1600–2400 µg/day). The symptoms of asthma and the lung function were assessed at baseline and on the 28th, 56th and 70th day of treatment, whereas the levels of cortisol and adrenocorticotropic hormone (ACTH) in the morning were measured at baseline and on the 28th and the 56th day of treatment.ResultsIn all patients, the control of asthma symptoms, measured with Asthma Control Test questionnaire, improved from the mean score of 9.4 to 19.8 in 70 days. In 4 subjects force expiratory volume in 1 s improved gradually through the entire study reaching a mean improvement of 585 ml in 70 days. The ACTH levels were normalized in 3 patients after 28 days of observation and in all patients after 56 days. The cortisol level was normalized in 4 patients after 28 days and in another subject after 56 days of treatment with ciclesonide.ConclusionsSwitching from prednisone to very high doses of ciclesonide normalized the hypothalamic-pituitary adrenal axis function and also improved the disease control and the lung function in these 5 patients with difficult asthma.

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Budesonide administered using chlorofluorocarbon and hydrofluoroalkane pressurized metered-dose inhalers: pharmacokinetics, pharmacodynamics and clinical equivalence

Cited by 3 publications

References 0 publications

Effect of salmeterol/fluticasone combination on the dynamic changes of lung mechanics in mechanically ventilated COPD patients: a prospective pilot study

Effect of salmeterol/fluticasone combination on the dynamic changes of lung mechanics in mechanically ventilated COPD patients: a prospective pilot study

Real-time analysis of gene regulation by glucocorticoid hormones

Switching from systemic steroids to ciclesonide restores the hypothalamic pituitary-adrenal axis

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